Collaborative Research: RUI: Regulation of the transition from primary to secondary ovarian follicle development by androgens in a teleost model

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Production of a fertilizable vertebrate egg is a complex process in which a small and relatively unspecialized cell, the oocyte, is provisioned with a variety of maternal materials that support fertilization and early embryonic development. Thus, many aspects of "egg quality", the term used to describe an egg that can be successively fertilized and lead to a viable offspring, are determined relatively early. The project will use ovaries from a non-mammalian vertebrate model to determine how early oocyte growth is regulated by hormones. Because of the conserved nature of egg development in vertebrates, the research will improve fundamental knowledge of egg development in vertebrates, including humans and agriculturally important animals, and may lead to the development of improved methods to overcome reproductive dysfunction of captive-reared fish in conservation and commercial aquaculture. The project will integrate research and education by recruiting undergraduate and graduate students from California State University Fullerton, a Hispanic Serving Institution, to work with a diverse group of scientists from the University of Washington, and with researchers from a federal agency. The goal is to train the next generation of scientists how to apply molecular tools, bioinformatics, and histology to biological questions while gaining an in-depth understanding of animal physiology, endocrinology, and reproduction. The research will be presented to the scientific community and to the public via established partnerships to provide trainees with service-learning experience.The basic physiology of female teleost reproduction, particularly during the later stages of oogenesis (e.g., vitellogenesis, maturation, ovulation) is fairly well understood. By contrast, comparatively little is known about the transition into puberty. In the ovary, this occurs when the primary growth ovarian follicles (containing developing oocytes) are recruited into secondary growth. Using a well-characterized in vitro model using coho salmon ovarian explants, the investigators have shown that 11-ketotestosterone (11KT), a teleost-specific aromatizable androgen, promotes the development of primary and early secondary ovarian follicles, associated with identification via RNA-Seq of altered mRNA levels of hundreds to thousands of genes, depending on stage. These changes are consistent with altered hormonal signaling pathways, tissue remodeling, and the progression to an early secondary ovarian follicle phenotype. The project will further explore the hypothesis that androgens are essential for early ovarian follicle by exploiting advances in proteomics, quantitative steroid biochemical analyses and the availability of homologous recombinant gonadotropins to: characterize the major endogenous androgens present in the female coho salmon during the onset of puberty; characterize androgen receptors; document the development-related changes in ovarian follicle proteins using cutting-edge proteomics; and explore the potential roles of gonadotropins in regulating previtellogenic ovarian follicle development.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.